Long-term consequences of HIV infection and its treatment appear to place the growing number of older HIV- infected adults at premature risk for disturbances of bone metabolism. HIV-infected adults are 3-4 times more likely to develop osteoporosis than their HIV-uninfected counterparts, and reported fracture rates are 30%-70% higher among HIV-infected persons. Body composition is an important factor in bone health, and body composition may be particularly affected in the setting of HIV infection as a result of the virus itself, specific antiretroviral drugs and restoration to health. HIV infection has been shown to differentially affect subcutaneous adipose tissue with greater decreases in the lower limbs. How this might affect bone health is unclear. Alterations in adipocyte differentiation in th lower limbs in the setting of HIV may affect bone metabolism. Some studies in HIV-uninfected persons suggest that fatty infiltration in the bone marrow (due to preferential differentiation fro a common marrow progenitor cell to adipocytes rather than osteoblasts) may lead to reduced bone formation, resulting in osteoporosis. While there is evidence that increased marrow fat, like low bone mineral density (BMD), predicts vertebral fracture in the elderly, and data suggest a relationship between increased marrow adiposity and bone loss, this area of investigation has been virtually unexplored in HIV- infected populations. Despite the high prevalence of disorders of bone and fat metabolism in HIV-infected individuals, little is known about how changes in regional body composition affect bone metabolism in this population. We propose: (1) To determine the relationship between regional fat changes and BMD among HIV- infected women compared with uninfected women; (2) To examine the relationship between adipokines and BMD in HIV-infected women; and (3) To conduct an exploratory investigation of the relationship between intravertebral marrow fat and BMD in HIV-infected women. Aims 1 and 2 of the proposed study will leverage the existing and ongoing data collected as part of the largest cohort study of HIV-infected women in the United States, the Women's Interagency HIV Study (WIHS), and specifically HIV-infected and uninfected women participants of the WIHS Metabolic Substudy (WIHS MS), a prospective study which performs rigorous metabolic testing including DXA scans to quantify regional fat and bone density measurements. Aim 3 will involve the collection of primary data in an exploratory investigation into bone marrow fat using magnetic resonance spectroscopy in a subset of WIHS MS women. The proposed study will allow the candidate to conduct high quality research in a timely and cost-effective manner, and examine the mechanism by which HIV-associated fat changes might affect bone loss in HIV-infected women. PUBLIC HEALTH RELEVANCE: Long-term consequences of HIV infection and its treatment, particularly disturbances of bone metabolism, are emerging concerns given the growing numbers of older adults living with HIV. The proposed study examines how body fat alterations due to HIV infection and its treatment affect bone metabolism and explores the novel role of fatty infiltration of bone marrow in bone disease development. Identification of the mechanisms underlying these associations may have important implications for bone density screening and preventive interventions for reduced BMD in HIV-infected women.